This invention relates to gene therapy methods for treating hemoglobinopathies.
The major form of adult human hemoglobin, HbA, consists of a tetramer of two .alpha.-globin chains and two .beta.-globin chains (.alpha..sub.2.beta..sub.2). Hemoglobinopathies, such as sickle cell anemia and .beta..sup.0 -thalassemia, are caused by a failure to produce normal levels of .beta.-globin. Hemoglobin A.sub.2 (HbA.sub.2), which consists of a tetramer of two .alpha.-globin chains and two .beta.-globin chains (.alpha..sub.2.delta..sub.2), is produced in low amounts in most sickle cell patients and in normal adults (2-3% of total hemoglobin) (Steinberg et al., Blood 78:2165, 1991). HbA.sub.2 is a potent inhibitor of the sickle hemoglobin (HbS; .alpha..sub.2.beta..sup.s.sub.2) polymerization characteristic of sickle cell anemia (Nagel et al., Proc. Natl. Acad. Sci. USA 76:670, 1979), and shares some functional activity with HbA.